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Outer Hair Cell Lateral Wall Structure Constrains the Mobility of Plasma Membrane Proteins


Nature’s fastest motor is the cochlear outer hair cell (OHC) in the mammalian inner ear. These cells can contract and elongate thousands of times per second. Slc26a5 (prestin) is the essential protein in the fast motor and resides in the plasma membrane of OHC lateral wall. Slc26a5 undergoes voltage-dependent conformational changes associated with the rapid changes in cell length to increase mammalian hearing sensitivity. However, it remains unclear how Slc26a5 transfers the force created to the entire cell. In this study, we show the importance of association between Slc26a5 and specialized membrane structures of the OHC lateral wall. Mobility of Slc26a5 was normally constrained in membrane-associated structures and disruption of these structures by a cholesterol depleting reagent and salicylate liberated Slc26a5 and four other heterologously expressed membrane proteins. These observations provide evidence that OHC lateral wall structure constrains the mobility of plasma membrane proteins and such membrane-associated structures are critical for Slc26a5’s functional roles. Our findings also shed light on other cellular motors across species and suggest a mechanism for cholesterol metabolic disorders in humans.


Vyšlo v časopise: Outer Hair Cell Lateral Wall Structure Constrains the Mobility of Plasma Membrane Proteins. PLoS Genet 11(9): e32767. doi:10.1371/journal.pgen.1005500
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005500

Souhrn

Nature’s fastest motor is the cochlear outer hair cell (OHC) in the mammalian inner ear. These cells can contract and elongate thousands of times per second. Slc26a5 (prestin) is the essential protein in the fast motor and resides in the plasma membrane of OHC lateral wall. Slc26a5 undergoes voltage-dependent conformational changes associated with the rapid changes in cell length to increase mammalian hearing sensitivity. However, it remains unclear how Slc26a5 transfers the force created to the entire cell. In this study, we show the importance of association between Slc26a5 and specialized membrane structures of the OHC lateral wall. Mobility of Slc26a5 was normally constrained in membrane-associated structures and disruption of these structures by a cholesterol depleting reagent and salicylate liberated Slc26a5 and four other heterologously expressed membrane proteins. These observations provide evidence that OHC lateral wall structure constrains the mobility of plasma membrane proteins and such membrane-associated structures are critical for Slc26a5’s functional roles. Our findings also shed light on other cellular motors across species and suggest a mechanism for cholesterol metabolic disorders in humans.


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